Journal
METALLOMICS
Volume 6, Issue 10, Pages 1931-1940Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4mt00122b
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Funding
- National Breast Cancer Fund [NC-10-69]
- Australian Research Council [DP120104035]
- University of Sydney International Scholarship (USydIS)
- Australia Alzheimer's Dementia Research Foundation (AADRF)
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Interactions between amyloid beta (A beta) and metal ions are thought to mediate the neuropathogenic effects of A beta in Alzheimer's disease. The construction of small molecules capable of synergistically chelating metal ions and recognizing A beta would allow new insights into the biology of this disease and provide a possible therapeutic approach. We report herein the synthesis and biological evaluation of tetraazamacrocycle-(G)KLVFF hybrids and their metal complexes. The results obtained from ThT and bis-ANS extrinsic fluorescence assays, tyrosine intrinsic fluorescence assay and proteolytic assay imply complex, multifaceted structure-activity relationships in the interaction of these conjugates with Ab. Many of the compounds tested rescued cells from A beta-induced cytotoxicity. The attendant simplicity and ready diversification of the synthesis of these conjugates makes them attractive for further investigation.
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